Study for Evaluation of Murlentamab (GM102) Anti-tumoral Activity in Colorectal Cancers

Inclusion Criteria: * Histologically confirmed metastatic or locally advanced colorectal adenocarcinoma. * Having failed the previous line of treatment for locally advanced or metastatic disease and having received at least two systemic chemotherapy regimens for metastatic colorectal cancer; adjuvant regimen can be considered as one chemotherapy regimen for metastatic disease if the participant had disease recurrence within 6 months of completion. * At least one of the tumor sites amenable to core needle biopsy (may not be the site of disease for measuring antitumor response). Patient must agree to this pre-treatment biopsy and on the principle of a second biopsy under treatment; however, if eventually the second biopsy cannot be performed, patients will continue on the study and will be considered evaluable for efficacy. * Available archived CRC tumor tissue sample * At least one measurable lesion (superior or equal to 1.0 cm longest diameter or superior or equal to 1.5 cm in short axis for malignant lymph nodes) based on RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 on the screening CT-scan. * Written Informed Consent forms signed. * Willing and able to comply with the trial requirements. * Covered by healthcare insurance in accordance with local requirements. * For cohort I (single agent GM102) only: refractory patients, having exhausted all therapeutic options. * For cohort II (GM102 in combination with trifluridine/tipiracil) only: patients eligible for trifluridine/tipiracil who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-Vascular Endothelial Growth Factor (anti-VEGF) agents, regorafenib and anti-Epithelial Growth Factor Receptor (anti-EGFR) agents. Patients must have received at least 2 prior lines of standard chemotherapy for metastatic CRC. Exclusion Criteria: * Age \< 18 years old. * Eastern Cooperative Oncology Group (ECOG) performance status superior or equal to 2. * Life expectancy \< 12 weeks. * Major surgery or radiotherapy within 21 days prior to Cycle 1 Day 1 or anticipation of needing such procedure while receiving study treatment. * Known or symptomatic brain metastasis (other than totally resected or previously irradiated and non-progressive/relapsing) or lepto-meningeal carcinomatosis. * Concurrent treatment with any other anticancer therapy (or investigational agent) or received any anticancer therapy (or investigational agent) within 4 weeks prior to first treatment. * Known severe anaphylactic or other hypersensitivity reactions to Investigational Medicinal Product (IMP) and/or its excipients. * Unresolved toxicity superior or equal to Grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 attributed to any prior therapies (excluding anemia, alopecia, skin pigmentation, and platinum induced neurotoxicity). * Serious concomitant illness, e.g. active infection requiring systemic antibiotic, antifungal or antiviral drug, or physical examination or laboratory abnormalities, that, in the opinion of the Investigator, would compromise protocol objectives. * Poor bone marrow reserve as defined by white blood cell \< 3.0 x 10E9/L, neutrophils \< 1.5 x 10E9/L or haemoglobin \< 9.0 g/dL or platelet count \< 100 x 10E9/L. * Poor organ function as defined by any one of the following: serum creatinine \> 1.5 x upper limit of normal (ULN), total bilirubin \> 1.5 x ULN or \> 2.5 x ULN if due to Gilbert's syndrome, AST and ALT \> 2.5 x ULN in the absence of liver metastasis or \> 5 x ULN in case of documented liver metastasis. * Severe New York Heart Association (NYHA) III and IV heart failure. * Pregnancy or breastfeeding. * Patient with reproductive potential who does not agree to use an accepted highly effective method of contraception - per investigator's judgment - during the study period and for at least 6 months following completion of study treatment. * Patient deprived of liberty by a judicial or administrative decision, patient admitted to a social institution or who is under a measure of legal protection, patient hospitalized without consent or who is in an emergency situation. * Known allergy to rodents. * Patients positive to Covid-19