• Histologically confirmed mismatch repair deficient or microsatellite instability high advanced stage colorectal cancer

• Measurable disease (per RECIST v1.1)

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1

• Age \> 18

• The patient must be able to swallow oral medication.

• Adequate organ function based on the following lab assessments:

‣ ANC must be ≥ 1500/mm3

⁃ platelet count must be ≥ 100,000/mm3

⁃ WBC count ≥ 2.5 × 109 /L

⁃ Hemoglobin must be ≥ 9 g/dL

⁃ Alkaline phosphatase ≤ 2.5× upper limit of normal (ULN) with the exception of patients with documented liver or bone metastases who should have ALP ≤ 5.0× ULN

⁃ AST and ALT ≤ 2.5× ULN with the exception of patients with documented liver metastases who may have AST and/or ALT ≤ 5.0× ULN

⁃ International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment with therapeutic anticoagulation

⁃ Total bilirubin ≤ 1.5× ULN (≤ 3× ULN if Gilbert syndrome present)

⁃ Serum albumin ≥ 2.8 g/dL or 28 g/L

‣ Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula) or creatinine ≤ 1.5× ULN

• No more than three cycles of prior fluoropyrimidine-based chemotherapy including folinic acid, fluorouracil, and oxaliplatin (FOLFOX); folinic acid, fluorouracil, and irinotecan (FOLFIRI); and, folinic acid, fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI) excluding adjuvant treatment

• Patients (male or female) of reproductive potential must agree to use an effective method of contraception (as discussed with treating physician) from the time consent is signed, during study therapy, and for at least 8 weeks after the last dose of study therapy.

• Patients who received no more than 1 cycle of pembrolizumab monotherapy will be still eligible to be enrolled in lead in phase of the trial