Investigate the Efficacy of Chemotherapy in Patients With Positive ctDNA After Surgery and Adjuvant Chemotherapy for a Stage III Colorectal Cancer

Inclusion Criteria: * Fully resected stage III or high-risk stage II colon or upper rectum adenocarcinoma previously treated by standard adjuvant chemotherapy or peri-operative chemotherapy (FOLFOX or CAPOX) for either 3 or 6 months based on local multidisciplinary meeting, and on TNCD recommendations * Positive ctDNA screening (methylation) and confirmation (NGS) on samples collected at the 3- or 6 months follow-up visit post-adjuvant chemotherapy * Patients ≥ 18 years and ≤ 80 years (provided the score of the G8 geriatric questionnaire is \>14 for patients 70 years or older) * Subjects with WHO performance status \< 2 * No documented disease using TAP CT-scanner and liver MRI in the case of contra-indication to dye contrast (or TEP-scanner may be also used in addition depending on physicians' choice and local availabilities). * Adequate haematological function: with neutrophils ≥ 1,500 /mm3, platelet count ≥ 100,000/mm3, hemoglobin ≥ 9 g/dL (5,6 mmol/l) Total bilirubin ≤ 1.5 x ULN (upper limit of normal) ASAT and ALAT ≤ 2.5 x ULN Alkaline phosphatase ≤ 2.5 x ULN Creatinine clearance ≥50 ml/min according MDRD (Modification of Diet in Renal Disease) * Available tumor sample for NGS analysis * Signed written informed consent obtained prior to any study specific procedures * Patient affiliated to a social security scheme Exclusion Criteria: * Patients already treated with trifluridine tipiracil or irinotecan in the past 5 years * Uncontrolled intercurrent illness * Previous malignancies other than adequately treated in situ carcinoma of the uterine cervix or basal or squamous cell carcinoma of the skin, unless there has been a disease-free interval of at least 3 years * Pregnant or breastfeeding women, women of childbearing age not having had a negative pregnancy test * Any known specific contraindication or allergy to the treatments used in the study† * Total or partial dihydropyrimidine dehydrogenase (DPD) deficiency (uracilemia \> 16ng/ml) * Known Gilbert's disease (UGT1A1\*28 genotype) * In case of concomitant use with St John's Wort related to irinotecan * In case of bowel obstruction according related to irinotecan * In case of recent concomitant treatment with brivudine, related to fluorouracil. * Participation to another interventional study for postoperative therapy * Persons deprived of liberty or under guardianship or incapable of giving consent * Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol or follow-up schedule.