Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma of the colon or rectum with metastatic disease
             measurable by RECIST v1.1 and not currently a candidate for oligometastatic definitive
             management

          -  Must have progressed or have demonstrated intolerance to first line therapy for
             metastatic disease. Individuals who recurred within 6 months of completion of
             oxaliplatin based adjuvant chemotherapy are also eligible.

          -  Subjects must have tissue from either the primary and/or metastatic deposit available
             for submission at enrollment

          -  Subjects must have measurable ctDNA, as detected by the Signatera ctDNA assay at time
             of sample analysis

          -  Subjects must have had molecular profiling to determine tumor RAS, BRAF and MMR/MSI
             status

          -  Subjects with known or suspected Gilbert's disease must be formally tested for
             UGT1A1*28 with results available to study team prior to treatment initiation

          -  Any clinically relevant (as deemed by the PI) adverse events related to prior
             therapies must have resolved to Grade 1 or less (CTCAE 5.0) at study enrollment

          -  Age ≥18 years

          -  ECOG performance status of 0-2

          -  Life expectancy of at least 6 months

          -  Adequate organ function

          -  Subjects must not have more than one active malignancy at the time of enrollment

          -  Women of childbearing potential must be using an adequate method of contraception to
             avoid pregnancy throughout the study and for at least 12 weeks after the end of
             protocol-specified treatment to minimize the risk of pregnancy.

          -  Males with female partners of child-bearing potential must agree to use
             physician-approved contraceptive methods throughout the study and should avoid
             conceiving children for 12 weeks following the last dose of the protocol-specified
             treatment.

          -  Written informed consent obtained from the subject and the subject agrees to comply
             with all the study related procedures

        Exclusion Criteria:

          -  Colorectal cancer known to be Microsatellite High (MSI-H), deficient in DNA mismatch
             repair genes (dMMR), or BRAF (V600E) mutated

          -  Females or males of childbearing potential who are unwilling or unable to use an
             acceptable method to avoid pregnancy for the entire study period and for at least 12
             weeks after the last dose of the protocol-specified treatment

          -  Females who are pregnant or breastfeeding

          -  History of any other disease, metabolic dysfunction, physical examination finding, or
             clinical laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of protocol therapy or that might affect the interpretation of
             the results of the study or that puts the subject at high risk for treatment
             complications, in the opinion of the treating physician

          -  Prisoners or subjects who are involuntarily incarcerated, or subjects who are
             compulsorily detained for treatment of either a psychiatric or physical illness

          -  Prior radiation therapy must have been completed 14 days prior to study entry

          -  Prior chemotherapy or biologic therapy must have been completed 21 days prior to study
             entry

          -  Known Dihydropyrimidine Dehydrogenase (DPD) deficiency