Inclusion Criteria:

          -  All subjects must have the ability to understand and the willingness to sign a written
             informed consent

          -  All patients must be able to take oral medications

          -  All patients must be deemed by investigator to have the initiative and means to be
             compliant with the study protocol (treatment and follow-up)

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  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

               -  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

          -  Tumors must have undergone expanded molecular profiling with a Clinical Laboratory
             Improvement Act (CLIA)-certified platform that evaluates, at a minimum, RAS, PIK3CA,
             PTEN and BRAF mutations status

          -  Documented RAS-mutated tumor without activating PIK3CA mutations or PTEN mutation
             (loss of PTEN or silencing)

          -  Measurable disease by RECIST 1.1 guidelines

          -  Last chemotherapy at least 3 weeks from initiation of study treatment

          -  No investigational agents within 4 weeks from initiation of study treatment

          -  Negative serum or urine beta-human chorionic gonadotropin (HcG) test (female patient
             of childbearing potential only) performed within 72 hours of prior to first study dose

          -  Absolute neutrophil count (ANC) >= 1500/mm^3 (to be performed within 28 days prior to
             day 1 of protocol therapy)

               -  NOTE: Growth factor is not permitted within 14 days of ANC assessment unless
                  cytopenia is secondary to disease involvement

          -  Platelets >= 75,000/mm^3 without transfusions (to be performed within 28 days prior to
             day 1 of protocol therapy)

          -  Hemoglobin (Hgb) >= 8 g/dL without transfusions (to be performed within 28 days prior
             to day 1 of protocol therapy)

          -  Total serum bilirubin < upper limit of normal (ULN) (to be performed within 28 days
             prior to day 1 of protocol therapy)

          -  Aspartate aminotransferase (AST) =< 2.5 x ULN if no liver metastases or =< 5 x ULN if
             liver metastases (to be performed within 28 days prior to day 1 of protocol therapy)

          -  Alanine aminotransferase (ALT) =< 2.5 x ULN if no liver metastases or =< 5 x ULN if
             liver metastases (to be performed within 28 days prior to day 1 of protocol therapy)

          -  Creatinine < 1.5 x ULN or creatinine clearance of >= 60 mL/min per the Cockcroft-Gault
             formula (to be performed within 28 days prior to day 1 of protocol therapy)

          -  Female of childbearing potential: negative urine or serum pregnancy test (to be
             performed within 28 days prior to day 1 of protocol therapy)

               -  If the urine test is positive or cannot be confirmed as negative, a serum
                  pregnancy test will be required

          -  Corrected QT (QTc) interval =< 480 ms (12 lead-electrocardiography [ECG]) (to be
             performed within 28 days prior to day 1 of protocol therapy)

          -  Left ventricular ejection fraction >= 50% as determined by multigated acquisition
             (MUGA) scan or echocardiogram (to be performed within 28 days prior to day 1 of
             protocol therapy)

          -  Normal eye examination (to be performed within 28 days prior to day 1 of protocol
             therapy)

          -  Women of childbearing potential must use highly effective methods of contraception
             throughout the study and for 4 months after study drug discontinuation

          -  Sexually active men must use a condom during intercourse while taking study drug and
             for 60 days after study drug discontinuation; a condom is required for vasectomized
             men to prevent delivery of study drug via seminal fluid

        Exclusion Criteria:

          -  Prior chemotherapy, biologic, targeted, or radiotherapy within 3 weeks prior to
             entering study or not recovered from grade >= 2 adverse events (AEs) due to agents
             administered more than 4 weeks earlier (except alopecia or neuropathy)

          -  Prior MEK inhibitor or prior TAS-102 therapy

          -  Use of other investigational drugs

          -  History or current evidence of retinal vein occlusion (RVO) or current risk factors
             for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of
             hyperviscosity, or hypercoagulability syndromes)

          -  History of retinal degenerative disease

          -  History of Gilbert's syndrome

          -  Previous or concurrent malignancy with the following exceptions:

               -  Adequately treated basal cell or squamous cell carcinoma of skin with adequate
                  wound healing prior to study entry

               -  In situ carcinoma of the cervix treated curatively and without evidence of
                  recurrence

               -  Primary malignancy completely resected and in complete remission >= 1 year

          -  History of acute coronary syndromes (including myocardial infarction, unstable angina,
             coronary artery bypass graft, coronary angioplasty, or stenting) < 6 months prior to
             screening

          -  Impaired cardiovascular function or clinically significant cardiovascular disease
             including any of the following: symptomatic congestive heart failure, clinically
             significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to
             screening except for atrial fibrillation and paroxysmal supraventricular tachycardia

          -  Uncontrolled arterial hypertension despite appropriate medical therapy (systolic blood
             pressure > 160 or diastolic blood pressure > 100)

          -  Neuromuscular disorders associated with elevated creatine kinase (CK, e.g.,
             inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, or spinal
             muscular atrophy)

          -  Started or planning to start on strenuous exercise regimen after first dose of study
             treatment (i.e., muscular activities, such as strenuous exercise, that can result in
             significant increase in plasma CK levels should be avoided while on trametinib
             treatment)

          -  Gastrointestinal (GI) disease or impairment of GI function (e.g., active ulcerative
             disease, uncontrolled nausea, vomiting, or diarrhea, malabsorption syndrome, or small
             bowel resection)

          -  Prior major surgery =< 3 weeks before study drug or not recovered from side effects of
             such procedure

          -  Ongoing grade >= 3 neuropathy

          -  Known hypersensitivity to any components of study drugs

          -  Prior intolerance to a fluoropyrimidine

          -  Any other condition that would, in the investigator's judgement, contraindicate the
             patient's participation in the clinical study due to safety concerns with clinical
             study procedures (e.g., infection/inflammation, intestinal obstruction, unable to
             swallow medications, social/psychological issues, etc.)

          -  Prospective participants who, in the opinion of the investigator, may not be able to
             comply with all study procedures (including compliance issues related to
             feasibility/logistics)