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.