Sequential Combined TAS-102 and Oxaliplatin Alternating with TAS-102 and Irinotecan (Sequential TASOXIRI) with Bevacizumab for Late-Line Metastatic Colorectal Cancer.

Inclusion Criteria: - Histologically confirmed stage IV colon cancer (AJCC 7th edition) that has progressed after standard therapy that included 5-FU, irinotecan, oxaliplatin and appropriate antibody therapy. Antibody therapy with bevacizumab and an anti-EGFR antibody, if RAS wild type, should have been given unless medical reasons have precluded their use. Participants who could not tolerate standard agents because of unacceptable, but reversible toxicity necessitating their discontinuation will be allowed to participate. - Participants who had received adjuvant chemotherapy and had recurrence during or within six months of completion of the adjuvant chemotherapy will be allowed to count the adjuvant therapy as one chemotherapy regimen for advanced disease. - Progression of disease must be documented on the most recent scan. - Presence of measurable disease - RAS mutation and MMR status must be determined (or tissue availability for testing if not already determined). - Age 18 years or older. - ECOG performance status 0-1. - Life expectancy of at least three months. - Participants with adequate organ function: 1. Absolute neutrophil count (ANC) > 1.5 x 109/L 2. Hemoglobin > 9 g/dL 3. Platelets (PLT) > 70 x 109/L 4. AST/ALT < 5 x ULN 5. Albumin within normal limits for institution - Women who are nursing and discontinue nursing prior to enrollment in the program. - Ability to take oral medication (i.e., no feeding tube). - Participant able and willing to comply with study procedures as per protocol. - Participant able to understand and willing to sign and date the written voluntary informed consent form (ICF) at screening visit prior to any protocol-specific procedures. Exclusion Criteria: - Participants who have previously received TAS-102. - Grade 3 or higher peripheral neuropathy (functional impairment). - Inability to tolerate irinotecan previously (due to uncontrolled diarrhea) - There are no specific exclusions for bevacizumab. Bevacizumab should be given unless there are specific contraindications per the treating investigator, which should be stated. If UPC is >1.0 (as above) hold bevacizumab until proteinuria resolves and then start bevacizumab. - Symptomatic CNS metastases requiring treatment. - Other active malignancy within the last three years (except for non-melanoma skin cancer or a non-invasive/in situ cancer). - Pregnancy or breast feeding. - Current therapy with other investigational agents. - Active infection with body temperature > 38°C due to infection. - Major surgery within prior four weeks (the surgical incision should be fully healed prior to drug administration). - Any anticancer therapy within prior two weeks of first dose of study drug. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS-102. - Current therapy with other investigational agents or participation in another clinical study or any investigational agent received within prior four weeks. - Grade 3 or higher hypersensitivity reaction to oxaliplatin or irinotecan, or grade 1-2 hypersensitivity reaction to oxaliplatin not controlled with pre-medication. - Has unresolved toxicity of greater than or equal to Common Terminology Criteria for Adverse (CTCAE) Grade 2 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum-induced neurotoxicity).