• Signed and dated patient informed consent form and willingness to comply with all study procedures and availability for the study duration,

• Age ≥ 18 years,

• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1, and 2,

• Histologically confirmed colorectal adenocarcinoma,

• Documented metastatic disease not suitable for complete surgical resection,

• Disease progression per iRECIST criteria (i.e., iCPD: immune confirmed PD) during monotherapy with anti-PD1 monoclonal antibody or less than 6 months after the discontinuation of anti-PD1 monoclonal antibody

• Disease progression during, after, or patients who are intolerant or have contraindications to approved standard therapies for the metastatic disease, which must include at least: • Fluoropyrimidine, oxaliplatin, and irinotecan, • Anti-EGFR therapy if wild-type RAS, • Anti-VEGF therapy,

• At least one measurable lesion as assessed by CT-scan or magnetic resonance imaging (MRI) according to RECIST 1.1 and feasibility of repeated radiological assessments,

• dMMR and/or MSI tumor status defined by: - Loss of MMR protein expression using immunohistochemistry with four (anti-MLH1, anti-MSH2, anti-MSH6, and anti-PMS2) antibodies, - and/or ≥ two unstable markers by pentaplex polymerase chain reaction (BAT-25, BAT-26, NR-21, NR-24, and NR-27), NB: In case of loss of expression of only one MMR protein immunohistochemistry, it is necessary to confirm the tumor is MSI using pentaplex PCR.

• NB: In cases with two unstable markers, comparison with matching normal tissue is required.

• NB: Agreement of the Sponsor (GERCOR) is mandatory to include the patient (the patient's file will be verified to confirm MSI/dMMR status before inclusion \[an anonymized fax\] and confirmation of a patient's allocation will be sent by mail to the Investigator within 24h).

⁃ For all patients, a new biopsy must be performed to obtain fresh anti-PD1 resistant tumor tissue prior to study treatment initiation,

⁃ For all patients, archival formalin-fixed paraffin-embedded tissue (FFPE) blocks and/or FFPE unstained slides (minimum of 30 positively charged slides representative of tumor tissue and non-tumor adjacent prior to anti-PD1 therapy (i.e., primary or metastatic site naïve of immunotherapy) must be submitted to the central laboratory,

⁃ Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 7 days prior inclusion: - Adequate hematological status (White blood cell \> 2000/μL; o Neutrophils \> 1500/μL; Platelets \> 100.000/μL; Hemoglobin \> 10.0 g/dL; - Adequate renal function: Serum creatinine level \< 120 μM; Clearance \> 50 ml/min (Modification of the Diet in Renal Disease \[MDRD\] or Cockcroft and Gault, - Adequate liver function: Serum bilirubin ≤ 1.5 x upper normal limit (ULN); Alkaline phosphatase (ALP) ≤ 3.0 x ULN; Alanine aminotransferase (ALT) ≤ 3.0 x ULN; Aspartate aminotransferase (AST) ≤ 3.0 x ULN; Hemostasis: Prothrombin time (PT)/International normalized ratio (INR) and activated partial PT (aPTT) ≤ 1.5 x ULN unless participants are receiving anticoagulant therapy and their INR is stable and within the recommended range for the desired level of anticoagulation,

⁃ Females of childbearing potential must have negative serum pregnancy test within 7 days before starting study treatment,

⁃ Women of childbearing potential should use effective contraception during treatment and at least 5 months thereafter.

⁃ Registration in a national health care system (Protection Universelle Maladie \[PUMa\] included)