['metastatic colorectal cancer']
['capecitabine', 'temozolomide', 'irinotecan', 'fluorouracil', 'leucovorin']

        Inclusion Criteria:

          -  Signed Informed Consent Form

          -  Histologically or cytologically confirmed adenocarcinoma of the colon and/or rectum,
             with MGMT promoter methylation and RAS mutation.

          -  Progressive disease on or after a first-line oxaliplatin containing chemotherapy
             regimen for mCRC with or without bevacizumab or other anti-angiogenic drugs. Patients
             must have received oxaliplatin-containing chemotherapy for ≥ 3 months. No more than
             one prior chemotherapy regimen for metastatic disease is allowed. 8

          -  Disease measurableRECIST v1.1

          -  Age ≥ 18 years and ≤ 75 years

          -  Life expectancy ≥ 12 weeks

          -  ECOG Performance Status of 0 1

          -  Adequate hematologic and end-organ function, defined by laboratory results obtained
             within 14 days prior to first administration: ANC ≥ 1500/μL Platelet count ≥
             100,000/μL Hemoglobin ≥ 9.0 g/dL Albumin ≥ 2.5 g/dL

          -  Total bilirubin ≤ 1.5 × the upper limit of normal (ULN)

          -  AST, ALT, and/or alkaline phosphatase ≤ 2.5 × ULN, with the following exceptions:
             Patients with documented hepatic metastases are eligible with AST, ALT, and/or
             alkaline phosphatase ≤ 5 × ULN. Patients with documented bone metastases are eligible
             with alkaline phosphatase ≤ 5 × ULN.

          -  Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min on the basis of the
             Cockcroft-Gault glomerular filtration rate estimation: (140 - age) × (weight in kg) ×
             (0.85 if female) 72 × (serum creatinine in mg/dL)

          -  INR and aPTT ≤ 1.5 × ULN

          -  documented agreement (by patient and/or partner) to use an effective means of
             contraception (e.g., surgical sterilization, a reliable barrier method, birth control
             pills, or contraceptive hormone implants) and to continue its use for the duration of
             the study and for 60 days for female patients or 150 days for male patients with
             partners of childbearing potential after the last infusion of study treatment.

          -  Consent to provide mandatory archival tumor tissue for biomarker testing

        Exclusion Criteria:

          -  Prior treatment with irinotecan and temozolomide

          -  Major surgical procedure within 4 weeks and radiotherapy within 2 weeks prior to Day 1
             Cycle 1

          -  Symptomatic hypercalcemia requiring continued use of bisphosphonate.

          -  Known clinically significant dihydropyrimidine 9 dehydrogenase deficiency

          -  Current severe, uncontrolled systemic disease Active infection requiring IV
             antibiotics

          -  History of heart failure of any New York Heart Association criteria or serious cardiac
             arrhythmia requiring treatment (except for atrial fibrillation and paroxysmal
             supraventricular tachycardia)

          -  History of myocardial infarction within 6 months prior to Cycle 1, Day 1, or history
             of unstable angina

          -  Known clinically significant liver disease,or current alcohol abuse

          -  History of bleeding diathesis or coagulopathy other than that due to anticoagulation
             therapy

          -  Patients receiving oral coumarin-derived anticoagulants

          -  Active haemoptysis within 30 days prior to Cycle 1, Day 1

          -  HIV infection

          -  Untreated/active CNS metastases (progressing or requiring anticonvulsants or
             corticosteroids for symptomatic control). Patients with a history of treated CNS
             metastases are eligible provided they meet all of the following criteria: Measurable
             disease outside the CNS as defined by RECIST v1.1.Radiotherapy completed ≥ 4 weeks
             prior to Cycle, 1 Day

          -  Pregnancy or lactation. Women of childbearing potential (including those who have had
             a tubal ligation) must have a documented negative serum pregnancy test within 14 days
             prior to Cycle 1, Day 1.

          -  Inability to take oral medications.

          -  Malignancies other than CRC within 3 years prior to randomization, with the exception
             of adequately treated basal or squamous cell skin cancer and carcinoma in situ of the
             cervix
      