Surgery is the main treatment method for colon cancer. About 50% of patients can be cured with surgery alone. For colon cancer with high-risk stage II or III after surgery, the current guidelines recommend 3-6 months after surgery. adjuvant chemotherapy to reduce the risk of recurrence and metastasis. However, for this part of the population, the overall benefit of adjuvant chemotherapy is limited, and different high-risk factors have different weights; some patients will still experience recurrence and metastasis even after receiving adjuvant chemotherapy. A number of previous studies have shown that patients with a positive ctDNA test on postoperative liquid biopsy without postoperative adjuvant therapy have a recurrence risk of 70-80%. Even if they receive adjuvant chemotherapy, the recurrence risk is significantly higher than that of ctDNA-negative patients. ctDNA has received increasing attention as a predictor of postoperative recurrence risk.

This study intends to randomly assign 1:1 to mFOLFOXIRI regimen adjuvant chemotherapy for 6 months and mFOLFOX6 regimen for colon cancer patients with postoperative high-risk stage II-III and liquid biopsy results within 1 month after surgery. Adjuvant chemotherapy was performed for 6 months, ctDNA was dynamically monitored after 3 months of treatment and at the end of adjuvant therapy. During the follow-up period, CEA was reviewed every 3 months, and chest, abdomen, and pelvis CT and ctDNA were reviewed every 6 months; the primary endpoint of the study was 2 years RFS, secondary endpoints included 3-year DFS, OS, safety and tolerability. Through intensive postoperative adjuvant therapy, we hope to screen colon cancer patients with high recurrence risk to receive adjuvant chemotherapy and improve the survival prognosis of ctDNA-positive colon cancer patients.

Inclusion Criteria:

1. Age 18-70 years old
2. Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.
3. ECOG performance status 0-1
4. Upfront surgery (R0 resection) and postoperative pathological stage II -III and the circulating tumor DNA (ctDNA) test results show that MRD was positive
5. Randomization must be within 8 weeks after surgery.
6. No distant metastasis after surgery
7. Appropriate organ function

Exclusion Criteria:

1. Postoperative CT scan showed distant meatstasis
2. Patients with postoperative obstruction or active bleeding
3. Other active malignant tumors in the past or at the same time (except for malignant tumors that have received curative treatment and have no disease for more than 5 years or carcinoma in situ that can be cured by adequate treatment)
4. The time from postoperative to start of adjuvant therapy has exceeded 8 weeks
5. Patients who have received neoadjuvant therapy
6. Active coronary artery disease, severe/unstable angina or newly diagnosed angina or myocardial infarction within 12 months prior to study participation
7. Thrombotic or embolic events within the past 6 months, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, deep vein thrombosis
8. Unstable or any medical condition that affects patient safety and study compliance
9. Subjects with known allergy to the study drugs or to any of its excipients.