Must have failed treatment with one regimen containing a fluoropyrimidine, oxaliplatin with or without bevacizumab for metastatic disease. All patients must have received a minimum of 6 weeks of the first-line regimen that included bevacizumab (if applicable), oxaliplatin and a fluoropyrimidine in the same cycle. Treatment failure is defined as radiologic progression during or < 6 months after the last dose of first-line therapy. No known allergy to 5-fluorouracil, oxaliplatin, or leucovorin Patients with colorectal cancer should have progressed on at least one fluorouracil plus irinotecan or oxaliplatin containing regimen fluoropyrimidine (IV 5-FU capecitabine, or S-1), platinum (cisplatin or oxaliplatin), Unless either drug is medically contraindicated, patients must have received oxaliplatin and irinotecan as part of standard metastatic chemotherapy regimens. KRAS Mutant CRC: Advanced KRAS mutant CRC who have progressed or are ineligible for both irinotecan and oxaliplatin based chemotherapy KRAS Wild Type CRC: Advanced KRAS wild type CRC who have progressed or are ineligible for both irinotecan and oxaliplatin based chemotherapy and who are relapsed or refractory to at least 1 prior systemic therapy that included an anti-EGFR antibody, such as cetuximab, panitumumab or others. The subject has a histologic or cytologic diagnosis of colorectal adenocarcinoma that is metastatic or unresectable and is refractory to or progressed (or relapsed) following a fluoropyrimidine, irinotecan, oxaliplatin, and bevacizumab; prior epidermal growth factor inhibitor therapy is required for patients with left-sided, RAS wild-type tumors; prior Food and Drug Administration (FDA)-approved PD-1 inhibitor therapy is required for patients with microsatellite instability high (MSI-H) colorectal cancer. Prior regorafenib or TAS-102 treatment is not required Colorectal cancer patients must have received prior therapy with each of following agents, if eligible: a fluoropyrimidine, oxaliplatin, irinotecean, and/or bevacizumab. Patients should have received no more than 3 systemic regimens in the metastatic setting. Progression on a prior line of therapy that contained a fluoropyrimidine and oxaliplatin or irinotecan for unresectable metastatic colorectal adenocarcinoma Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil, leucovorin (leucovorin calcium), irinotecan, or panitumumab HER2-positive gastric/GEJ cancer must have received prior trastuzumab, cisplatin (or carboplatin or oxaliplatin or investigational platinum agent) and 5-fluorouracil (5-FU)/capecitabine HER2-Positive Solid Tumor Specific Inclusion Criteria Patients must have had at least prior treatment with a fluoropyrimidine and either oxaliplatin or irinotecan. Prior treatment with, contra-indication to or refusal of a fluoropyrimidine, irinotecan, oxaliplatin and an anti-EGFR targeted therapy (if RAS wild-type [wt]) For metastatic colorectal cancers, patients starting maintenance capecitabine after a course of oxaliplatin or irinotecan based chemotherapy are eligible Patients must have received and progressed through or become intolerant to fluoropyrimidine, irinotecan, oxaliplatin, and bevacizumab; if RAS wild type, patients should have received and progressed or become intolerant to the above as well as cetuximab or panitumumab containing therapies; prior therapy with regorafenib and/or TAS 102 is allowed Patients with a known immediate or delayed hypersensitivity reaction or idiosyncrasy to talimogene laherparepvec or any of its components, capecitabine, fluorouracil (5-FU) and / or oxaliplatin are ineligible Patients must have progressed on, been intolerant of or refused prior oxaliplatin- and irinotecan-containing, fluorouracil-based, chemotherapeutic regimen and have disease that is not amenable to potentially curative resection; patients who have a known KRAS wild type tumor must have progressed, been intolerant of or refused cetuximab or panitumumab-based chemotherapy Patients must have previously received standard systemic therapy for their advanced cancer and have been either non-responders (progressive disease) or have recurred; specifically;\r\n* For patients with metastatic colorectal cancer, they must have had at least two systemic chemotherapy regimens that include fluorouracil (5FU), leucovorin, bevacizumab, oxaliplatin and irinotecan or have contraindications to receiving those medications\r\n* For pancreatic cancer, they must have received gemcitabine, 5FU and oxaliplatin or have contraindications to receiving those medications\r\n* Patients with non-small cell lung cancer (NSCLC) must have had appropriate targeted therapy as indicated by abnormalities in ALK, EGFR or expression of PDL-1; other patients must have had platinum-based chemotherapy\r\n* Patients with ovarian cancer or prostate cancer must have had approved first line chemotherapy Patients must be resistant to or intolerant of fluorouracil (5FU), oxaliplatin, irinotecan, bevacizumab and cetuximab/panitumumab (if RAS wild type) Prior therapy with oxaliplatin Colorectal patients must have received prior fluorouracil (5FU), irinotecan and oxaliplatin (any combination) or have a contraindication to receiving these agents mCRC with prior progression on standard multi-agent combination chemotherapy and regorafenib as a standard approved monotherapy; progression on prior regorafenib is required for inclusion in this clinical study; prior regimens may include fluorouracil/leucovorin calcium/oxaliplatin (FOLFOX) -/+ bevacizumab, folinic acid-fluorouracil-irinotecan (FOLFIRI) -/+ bevacizumab or -/+ cetuximab (if KRAS wild-type) or panitumumab (if KRAS wild-type); other prior regimens may include 5-FU or capecitabine -/+ bevacizumab, irinotecan -/+ cetuximab or panitumumab, FOLFIRI -/+ ziv-aflibercept or ramucirumab Patients must have received at least one prior line of therapy for the treatment of metastatic disease with a fluoropyrimidine in combination with oxaliplatin and/or irinotecan; patients with prior adjuvant therapy who progressed within 6 months of completion of treatment may be eligible Failure of first-line anti-cancer therapy with an oxaliplatin and bevacizumab-based regimen (either radiological documentation of disease progression or due to toxicity) or subsequent relapse of disease following first-line therapy; patients relapsing within 12 months of completing adjuvant fluorouracil, leucovorin calcium, oxaliplatin (FOLFOX) will also be considered eligible Patients must have an advanced solid tumor malignancy with no remaining standard treatment options or for whom single agent capecitabine is an acceptable therapy; patients with colorectal cancer must have progressed on at least one line of fluoropyrimidine containing therapy; receipt of either oxaliplatin or irinotecan in combination with a fluoropyrimidine is required in the front line setting for all colorectal cancer patients unless either of these agents are otherwise contraindicated in the opinion of the treating physician; prior regorafenib or TAS-102 therapy is not required PHASE II: Patients must have received and progressed on fluoropyrimidine or fluoropyrimidine based therapy; receipt of either oxaliplatin or irinotecan in combination with a fluoropyrimidine is required in the front line setting unless either of these agents are otherwise contraindicated in the opinion of the treating physician in which case a fluoropyrimidine only may be used; prior regorafenib or TAS-102 therapy is not required Subjects must have received at least one prior line of chemotherapy including an irinotecan or oxaliplatin-fluoropyrimidine-based systemic treatment for colorectal cancer Patients must have received last dose of either fluorouracil, oxaliplatin, leucovorin calcium, and irinotecan hydrochloride (FOLFIRINOX) based or gemcitabine/abraxane based chemotherapy for 4-8 cycles with last dose of therapy between 2-5 weeks of study enrollment, with no evidence of metastatic disease Patients must have progressed during or after first-line treatment for metastatic disease with oxaliplatin and fluoropyrimidines based chemotherapy (with failure within six months) or not be a candidate for oxaliplatin (i.e. neuropathy) Prior therapy with >= 1 prior systemic therapy over a period of at least 2 months (eg, at least two 4-week cycles of a regimen such as gemcitabine and nab-paclitaxel; or at least four 2-week cycles of a regimen such as fluorouracil/leucovorin calcium/oxaliplatin [FOLFOX], fluorouracil/irinotecan/leucovorin calcium/oxaliplatin [FOLFIRINOX], or folinic acid-fluorouracil-irinotecan [FOLFIRI]) Subjects have received two or more standard available therapies known to prolong survival and for which they would be considered eligible; at a minimum, such therapies should include regimens containing oxaliplatin and irinotecan in combination with a fluoropyrimidine (e.g., leucovorin calcium-fluorouracil-oxaliplatin [FOLFOX] and leucovorin calcium-fluorouracil-irinotecan hydrochloride [FOLFIRI] or their variants) 5FU and oxaliplatin are known to be safe to be administered in patients with such abnormal liver function tests Prior history of hypersensitivity reactions to oxaliplatin, bevacizumab, fluorouracil (5-FU) or capecitabine Part B dose expansion: Must have confirmed Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type colorectal cancer that is metastatic or recurrent and has failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant of irinotecan or oxaliplatin Prior therapy with a platinum chemotherapy (e.g. cisplatin, carboplatin, oxaliplatin) Must have completed 3 cycles of neo-adjuvant chemotherapy. Either capecitabine-oxaliplatin (CAPEOX) or leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) is allowed. Dose modifications are allowed, but all 3 cycles must have been completed. Previously treated with two prior regimens of systemic chemotherapy for metastatic or locally advanced, unresectable disease, including fluoropyrimidines (5-fluorouracil and/or capecitabine), oxaliplatin, and irinotecan\r\n* A maintenance regimen of 5-fluorouracil or capecitabine, with or without bevacizumab, should not be counted as a separate line of treatment\r\n* For patients who experienced disease recurrence during or within 6 months of completion of adjuvant chemotherapy with fluoropyrimidine and oxaliplatin, only one regimen of systemic chemotherapy for metastatic disease is required Known hypersensitivity to fluorouracil (5-FU), oxaliplatin, or other platinum agents Progression during or within 6 months after fluoropyrimidine, irinotecan, and oxaliplatin; for oxaliplatin-based therapy, failure of therapy will also include patients who progressed within 12 months of adjuvant therapy and patients who had oxaliplatin discontinued secondary to toxicity or allergic reaction; patients with a known history of Gilbert’s disease who cannot receive irinotecan or patients who are intolerant of irinotecan or fluoropyrimidine are eligible Known hypersensitivity to any of the components of PRI?724, fluorouracil (5?FU), oxaliplatin or bevacizumab Pathologically confirmed advanced, unresectable, or metastatic colon or rectal cancer who have had intolerance to or progression after a fluoropyrimidine, oxaliplatin, irinotecan, and cetuximab or panitumumab in the event of wild-type RAS/BRAF tumors\r\n* Of note, prior bevacizumab or regorafenib exposure is not mandated as some patients are deemed poor candidates for anti-angiogenesis therapy and never receive these agents Prior intolerance to a fluoropyrimidine Patients must have received at least 6 months fluorouracil (5-FU)- or gemcitabine-based treatments for pancreas cancer (fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin [FOLFIRINOX], fluorouracil, leucovorin calcium and oxaliplatin [FOLFOX], 5-FU+ nal-IRI [MM-398; nanoliposomal irinotecan], or 5-FU [including capecitabine], gemcitabine-based gemcitabine plus abraxane, gemcitabine monotherapy among others) Have received at least 1 treatment of either fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin (FOLFIRINOX) or gemcitabine/abraxane based regimens in the neoadjuvant setting; modifications of FOLFIRINOX including leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX), leucovorin calcium, fluorouracil, and irinotecan hydrochloride (FOLFIRI), fluorouracil (5FU) and capecitabine and modifications of gemcitabine/abraxane including single agents gemcitabine or abraxane are allowed Prior treatment with 5-fluorouracil, irinotecan or oxaliplatin Patients must have had prior first-line therapy with oxaliplatin-based fluoropyrimidine-containing chemotherapy and bevacizumab for metastatic colorectal cancer For the phase II portion, patients must have histologically and/or cytologically confirmed metastatic colorectal carcinoma that has progressed on, is intolerant of, or is inappropriate for all standard therapies; subjects must have been treated with a fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan and bevacizumab or have contraindication to such treatment; prior epithelial growth factor receptor (EGFR)-targeting agent (or contraindication to these drugs) is required for subjects with K-Ras wildtype tumors previously received at least 2 but no more than 4 lines of therapy, which must have included both an irinotecan and an oxaliplatin based regimen Histologically and/or cytologically confirmed and radiographically measurable KRAS and NRAS wild-type adenocarcinoma of the colon or rectum that is metastatic and/or unresectable; subjects must have been treated with a fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan and bevacizumab or have contraindication to such treatment Histologically and/or cytologically confirmed and radiographically measurable KRAS and NRAS wild-type adenocarcinoma of the colon or rectum that is metastatic and/ or unresectable; subjects must have been treated with a fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan and bevacizumab or have contraindication to such treatment; in addition, for the monotherapy MET Amplified cohort, subjects must have received prior treatment with anti-EGFR therapy (either panitumumab or cetuximab) Prior systemic regimens must include previously approved therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; an anti-VEGF therapy (if no contraindication); and if negative for KRAS, NRAS, and BRAF mutations and no contraindication, an anti-epidermal growth factor receptor (EGFR) therapy; and progressed after the last administration of approved therapy. Prior progression following a fluoropyrimidine-based therapy and progression following or intolerance to irinotecan and oxaliplatin, as well as anti-epidermal growth factor receptor (EGFR) therapy (e.g., panitumumab or cetuximab) for rat sarcoma viral oncogene homolog (RAS) wild-type patients Received first-line combination therapy containing oxaliplatin and fluoropyrimidine with or without bevacizumab for metastatic disease with documented evidence of disease progression during or after treatment completion The patient must have completed at least 4 months of adjuvant chemotherapy (i.e., FOLFOX, CapeOx, or other, such as 5-fluorouracil, leucovorin, oxaliplatin (FLOX), 5-fluorouracil/leucovorin (5FU/LV), capecitabine). Untreated for metastatic colorectal cancer or progression on any first line fluorouracil (5-FU) containing regimen (such as leucovorin calcium, fluorouracil, oxaliplatin [FOLFOX] or irinotecan, fluorouracil, leucovorin calcium [FOLFIRI]) Metastatic disease not amenable to surgical curative treatment and eligible to receive therapy with mFOLFOX6 (Leucovorin/5-Fluorouracil/Oxaliplatin) + bevacizumab. Histologically and/or cytologically confirmed and radiographically measurable adenocarcinoma of the colon or rectum that is metastatic and/or unresectable; subjects must have been treated with a fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan, and an anti-VEGF monoclonal antibody (bevacizumab, ramucirumab, or ziv-aflibercept), or have contraindication to such treatment Histologically confirmed colorectal cancer that is either clinically or histologically proven to be metastatic and has progressed on regimens containing a fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan, bevacizumab and an anti-EGFR antibody (if tumor is RAS wild-type), or where the treatment was not tolerated or contraindicated Intent to treat the patient with a leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) chemotherapy regimen containing fluorouracil (5-FU), leucovorin, and oxaliplatin according to clinical standard practice; the intent should be to dose oxaliplatin at 85 mg/m^2 on an every 2 week basis Prior treatment with oxaliplatin Has been previously treated with standard therapies, which must include, for Cohort A, fluoropyrimidine, oxaliplatin, and irinotecan, and for Cohort B, at least one line of systemic standard of care therapy: fluoropyrimidine + oxaliplatin or fluoropyrimidine + irinotecan +/- anti-VEGF/EGFR monoclonal antibody (mAb). Subjects have received two or more standard available therapies known to prolong survival and for which they would be considered eligible; such therapies should include regimens containing oxaliplatin and irinotecan in combination with a fluoropyrimidine if appropriate (e.g., FOLFOX and FOLFIRI or their variants) Has known hypersensitivity to fluorouracil (5FU), oxaliplatin, or other platinum agents. Patients may be treatment naïve, or may have received standard chemotherapy; including regimens containing a fluoropyrimidine, or oxaliplatin, or irinotecan, or regorafenib, or bevacizumab. Unless either drug is medically contraindicated, patients must have received oxaliplatin and irinotecan as part of standard chemotherapy regimens. (This includes adjuvant therapy.) Completion of at least 3 months of standard induction chemotherapy for locally advanced pancreatic carcinoma (LAPC), which may include fluorouracil/irinotecan/leucovorin calcium/oxaliplatin (FOLFIRINOX) or gemcitabine and nab-paclitaxel, within 6 weeks of enrollment Has been previously treated with fluoropyrimidine, irinotecan, and oxaliplatin Must have been previously treated with 1 line of therapy including a fluoropyrimidine plus an oxaliplatin-based regimen Progression following treatment with fluoropyrimidine/oxaliplatin/bevacizumab-regimen in the metastatic setting. Eligibility for the expansion cohort: Histologically or cytologically confirmed colon or rectal adenocarcinoma for which curative treatment does not exist; patients must have documented progression or intolerance to at least one prior regimen containing 5-fluorouracil or capecitabine and oxaliplatin Patients must have received at least 2 regimens containing 5-Fluorouracil,oxaliplatin, or irinotecan. Prior use of sorafenib, oxaliplatin, or fluorouracil (5FU) Prior systemic fluoropyrimidine therapy (unless given in an adjuvant setting and completed at least 6 months earlier); prior topical fluoropyrimidine use is allowed; prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil (fluorouracil) or known dihydropyrimidine dehydrogenase (DPD) deficiency Progression on, or intolerance of, or ineligibility for all standard therapies (including regimens containing fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and an anti-epidermal growth factor receptor [EGFR] antibody [where appropriate]); patients who are intolerant of, or ineligible for 5-FU, oxaliplatin, and/or the combination of both will be excluded Patients who are intolerant of, or ineligible for 5-FU, oxaliplatin, and/or the combination of both Must have metastatic colorectal cancer or pancreatic cancer with stable disease after first line chemotherapy or patients with colorectal or pancreatic cancer who have progressed with standard chemotherapy options\r\n* Standard chemotherapy examples for metastatic colorectal cancer include 5-FU (fluorouracil)/capecitabine with either oxaliplatin or irinotecan based regimen with or without bevacizumab or cetuximab\r\n* Standard chemotherapy examples for metastatic pancreatic cancer include gemzar based regimen or FOLFIRINOX (5-FU, oxaliplatin, and irinotecan) Progression during or within 6 months following administration of a standard regimen for treatment of metastatic disease that included oxaliplatin with any of the following agents with or without bevacizumab:\r\n* 5-fluorouracil (5-FU) with or without leucovorin or levoleucovorin\r\n* Capecitabine\r\nNOTE: in patients receiving FOLFOX, oxaliplatin is sometimes discontinued due to toxicity or as part of maintenance therapy strategy; if such patients progress while on 5-FU alone, they are eligible for this trial; as an example, a patient who is begun on FOLFOX or CapeOx (with or without bevacizumab), whose oxaliplatin is held for neurotoxicity and who is switched to capecitabine monotherapy or capecitabine with bevacizumab, would be considered to have had ONE prior therapy OR patients who develop metastatic disease within 9 months of adjuvant FOLFOX for stage II or III colon cancer Prior progression on or intolerance to treatment with a fluoropyrimidine and oxaliplatin; recurrence of disease within 6 months from the completion of adjuvant therapy with both a fluoropyrimidine and oxaliplatin is considered progression Have received prior treatment for metastatic disease with oxaliplatin-based regimen and either:\r\n* Had disease progression OR\r\n* Had stable disease OR\r\n* Discontinued oxaliplatin due to neuropathy Main inclusion Criteria:\n\n 1. Male or female, at least 18 years of age at the time of informed consent\n\n 2. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1\n\n 3. Histologically or cytologically confirmed, locally advanced or metastatic colorectal\n cancer (CRC) that is documented to be without Kirsten rat sarcoma (KRAS) or\n Neuroblastoma rat sarcoma (NRAS) gene mutations (i.e. tumors must express the KRAS and\n NRAS wild type (WT), exon 2, 3 and 4).\n\n 4. Failed* treatment for locally advanced or metastatic disease with first-line\n combination therapy of oxaliplatin and a fluoropyrimidine, with or without\n bevacizumab, during treatment or < 3 months after the last dose of first-line therapy\n and within < 3 months of C1/D1.\n\n Patients who discontinued first-line therapy due to toxicity may be enrolled provided\n progression occurred < 6 months after the last dose of the first-line therapy regimen.\n\n or Failed* adjuvant therapy with combination therapy of oxaliplatin and a\n fluoropyrimidine during treatment or within < 6 months after the last dose of\n oxaliplatin and within < 6 months of C1/D1.\n\n - Failure is defined as radiologic progression\n\n 5. Eligible for FOLFIRI\n\n 6. Measurable disease according to RECIST v1.1\n\n Main exclusion Criteria:\n\n 1. Prior therapy with anti-EGFR antibodies, anti-EGFR small molecule inhibitors or\n irinotecan (CPT-11)\n\n 2. Any antineoplastic agent (standard or investigational) within 4 weeks prior to C1/D1\n\n 3. Significant gastrointestinal abnormalities\n\n 4. Patients with a significant cardiovascular disease or condition\n\n 5. Abnormal hematologic, renal or hepatic function Patients must have had 16 to 20 weeks of first-line therapy with oxaliplatin, and/or irinotecan-based fluoropyrimidine-containing chemotherapy plus bevacizumab No known hypersensitivity to any of the following agents: oxaliplatin, cisplatin, capecitabine, 5-flurouracil, docetaxel, or irinotecan Patient must have received only one cycle of the following regimens (with or without epirubicin) during the pre-registration time period and no other therapy for gastric or gastroesophageal junction cancer:\r\n* Oxaliplatin, and capecitabine\r\n* Oxaliplatin, and fluorouracil\r\n* Cisplatin, and capecitabine\r\n* Cisplatin, and fluorouracil Known hypersensitivity to 5-fluorouracil, leucovorin, or oxaliplatin (Arm: idelalisib + mFOLFOX6), their metabolites, or formulation excipients Previous treatment with fluoropyrimidine-, oxaliplatin- and irinotecan- based chemotherapy, an anti-VEGF therapy (if no contraindication) and if KRAS wild type and no contraindication, an anti-EGFR therapy. Patients must have received prior fluoropyrimidine, oxaliplatin and irinotecan-based therapy for their disease and had progression or intolerance to these agents that resulted in treatment discontinuation Have received at least 3 months ,of neoadjuvant, adjuvant, or perioperative chemotherapy, including a fluoropyrimidine and either oxaliplatin or irinotecan or both for subjects with initial Stage IV CRC which were treated with surgery with curative intent for both primary and metastatic lesions. The total chemotherapy administered, including that administered prior to and after liver resection, should not exceed 9 months. OR Have received surgery with curative intent for primary CRC and at least 3 months ,of neoadjuvant, adjuvant, or perioperative chemotherapy for the primary tumor, including a fluoropyrimidine or a fluoropyrimidine and either oxaliplatin or irinotecan or both For subjects with liver metastases developing > 6 months after completing treatment for primary CRC and having undergone surgery with curative intent for liver metastases, a second course of chemotherapy lasting at least 3 months needs to be administered, including a fluoropyrimidine and either oxaliplatin or irinotecan or both. The second course of chemotherapy should not exceed 9 months. For subjects who developed liver metastases >/=6 months after completing treatment for primary CRC and having undergone surgery with curative intent for liver metastases, a second course of chemotherapy is not permitted unless initial adjuvant therapy consisted of fluoropyrimidine monotherapy. Subjects who received fluoropyrimidine alone must have received a second course of chemotherapy with fluoropyrimidine and either oxaliplatin or irinotecan or both, which should not exceed 9 months.For subjects with initial Stage I or II disease, no chemotherapy is required for a primary CRC lesion treated with surgery with curative intent. These subjects must receive chemotherapy for the treatment of liver metastases (which were also treated with surgery with curative intent), which must last at least 3 months, including a fluoropyrimidine and either oxaliplatin or irinotecan or both. The total course of chemotherapy should not exceed 9 months. Subjects with pathologically confirmed colorectal carcinoma that is metastatic or unresectable and which is refractory to standard therapy. To be considered refractory, a subject must have experienced progression (or intolerance) after treatment with standard approved regimens including, oxaliplatin, irinotecan flouropyrimidine, bevacizumab, and cetuximab or panitumumab if KRAS wildtype. Patients with unresected metastases from colorectal cancer; patients may be either untreated with chemotherapy or currently receiving first-line 5-FU based chemotherapy (folinic acid-fluorouracil-irinotecan hydrochloride [FOLFIRI], capecitabine-irinotecan hydrochloride [CAPIRI], fluorouracil-leucovorin calcium-oxaliplatin [FOLFOX], or capecitabine-oxaliplatin [CAPOX] with or without bevacizumab) within 10 months of beginning ADAPT therapy with at least stable disease radiographically; patients who received prior adjuvant chemotherapy with 5-FU, capecitabine, or FOLFOX are eligible if adjuvant therapy was completed greater than 6 months ago Patients must have progressed on or been intolerant of prior oxaliplatin and irinotecan-containing chemotherapeutic regimen and have disease that is not amenable to potentially curative resection; patients who have a known Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type tumor must have progressed or been intolerant to cetuximab or panitumumab-based chemotherapy Refractory to or intolerant of standard systemic therapy, including having received two or more standard available therapies known to prolong survival for which s/he was eligible, including leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX) or leucovorin calcium, fluorouracil, and irinotecan hydrochloride (FOLFIRI) with or without bevacizumab, aflibercept, cetuximab or panitumumab - fluoropyrimidine - oxaliplatin: Patients treated with oxaliplatin in adjuvant setting should have progressed within 6 months of completion of adjuvant therapy or they must have been treated with oxaliplatin for metastatic disease Subjects with advanced/metastatic Colorectal Cancer(CRC) who have failed or been intolerant to both irinotecan- and oxaliplatin- based regimens Failure of or intolerance to 5-FU, Oxaliplatin, and Irinotecan Patients with pathologically confirmed colon or rectal cancer who have received and progressed or failed following a fluoropyrimidine, irinotecan, and oxaliplatin based chemotherapy regimens will be eligible for this study; patients who have a known Kirsten rat sarcoma viral oncogene homolog (KRAS)/v-raf murine sarcoma viral oncogene homolog B (BRAF) wild type tumor should have progressed or failed following cetuximab or panitumumab based chemotherapy; prior bevacizumab or regorafenib exposure is not mandated on this study as some patients are deemed poor candidates for anti-angiogenesis therapy and never receive these agents Prior intolerance to fluorouracil (5-FU) or oxaliplatin, excluding severe neuropathy that reversed to grade 2 or less Refractory disease defined as: \r\n* Prior treatment with fluoropyrimidine, oxaliplatin, irinotecan, and anti-epidermal growth factor receptor (EGFR) therapy if v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) wildtype for colorectal adenocarcinoma and\r\n* Prior treatment with fluoropyrimidine and oxaliplatin for small bowel adenocarcinoma Patient must be refractory to or intolerant of prior therapy with a fluoropyrimidine, oxaliplatin, irinotecan, and/or anti-angiogenic therapy; patients with v-Ki-ras2 Kirsten rat sarcoma (K-RAS) wild type tumors must have received an epidermal growth factor receptor (EGFR) inhibitor such as cetuximab or panitumumab Up to 12 patients with metastatic colorectal cancer with a history of progression or recurrence following prior fluoropyrimidine, irinotecan and platinum containing regimens as well as bevacizumab. In addition, patients with Kras wild type tumor must have received at least one EGFR blocker. Participants who received prior chemotherapy that included cisplatin, carboplatin, or oxaliplatin Patients who had received Oxaliplatin within 12 months prior to diagnosis of metastatic disease. Dose limiting toxicity with previous adjuvant 5-FU or oxaliplatin chemotherapy. Known hypersensitivity to BGJ398, fluorouracil, oxaliplatin, irinotecan or to any of the excipients Histologically or cytologically confirmed adenocarcinoma of the rectum that was clinically staged T3, T4 or node-positive (defined as >= N1 per American Joint Committee on Cancer [AJCC] 7th edition) that was treated with the following treatment with curative intent:\r\n* Curative surgical resection\r\n* Pre- or post-operative chemoradiation; and at least 3 months of combined adjuvant OR neoadjuvant systemic chemotherapy (equivalent to 6 cycles of leucovorin calcium, fluorouracil, and oxaliplatin [FOLFOX] or infusional fluorouracil [5FU]) completed or have developed intolerance to a course of oxaliplatin- or irinotecan-based frontline therapy at Screening Scheduled for oxaliplatin treatment in modified leucovorin calcium, fluorouracil and oxaliplatin regimen (mFOLFOX)6-based chemotherapy regimen Anticipated 2 or more subsequent chemotherapy infusions of either carboplatin or oxaliplatin at the time of study registration; NOTE: the dose of carboplatin or oxaliplatin, choice of other chemotherapy, and other ancillary treatment, such as antiemetics, will be left to the discretion of the treating healthcare provider Prior carboplatin or oxaliplatin hypersensitivity reaction Scheduled to receive concurrent administration of fluoropyrimidine chemotherapy (fluorouracil [5-FU] or capecitabine) during radiation therapy Presence of any contraindications for nal-IRI, irinotecan, 5-FU, leucovorin, oxaliplatin Patients who qualify for oxaliplatin-based chemotherapy (in the adjuvant or metastatic setting) and are likely to receive at least 3 months of oxaliplatin There are no restrictions on the amount or types of prior therapy; eligible patients must be receiving ongoing chemotherapy with an oxaliplatin containing-regimen which is planned to continue for at least one month following enrollment in this trial; any dose or schedule of oxaliplatin administration is allowed as long as patients have self-reported taste disturbance that has either: 1) developed since the initiation of oxaliplatin-based therapy, or 2) a pre-existing, treatment-induced taste disturbance has subjectively worsened since initiating oxaliplatin-based therapy Will receive concurrent administration of chemotherapy (fluorouracil [5-FU], capecitabine, cisplatin, oxaliplatin, carboplatin, and/or mitomycin C) during pelvic RT Clinically evident HSR to oxaliplatin, with symptoms of flushing, urticaria, pruritus, rash, and/or dyspnea without bronchospasm that emerge during or shortly after of oxaliplatin infusion Responding (complete or partial) or stable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria while undergoing treatment with oxaliplatin containing regimen or need to resume an oxaliplatin based regimen in the setting of well-documented recent oxaliplatin hypersensitivity reaction Prior treatment with oxaliplatin.