The main cause of recurrence after surgical treatment of colorectal cancer is distant metastasis. Neoadjuvant chemotherapy has potential benefits of improving the effectiveness of chemotherapy. Preoperative chemotherapy may eradicate microscopic metastatic cancer cells earlier than adjuvant chemotherapy, reduce cancer cell spillage during surgery, and lessen the invasiveness of surgical resection. The FOLFOXIRI regimen has been shown to have a high objective efficiency in advanced colorectal cancer. This phase II trial is to explore the pathological remission rate and safety of stage II/III locally advanced colon cancer with high risk of recurrence to FOLFOXIRI regimen of neoadjuvant chemotherapy alone.

Inclusion Criteria:

• Age: 18-75 years old; Sex: Male or female;
• WHO performance status of 0, 1 or 2
• Histologically proven colorectal carcinoma (defined as cancer that is located >10 cm from the anal verge by endoscopy)
• Unequivocal radiological evidence of locally advanced cancer based on thin slice spiral CT [defined as T4a/b or (and) N2 / fused lymph nodes or (and) positive extramural vascular invasion (EMVI +) or (and) circumferential resection margin (CRM) ≤ 2mm].
• No distant metastases (distant organ or (and) distant lymph node metastases) assessed by CT scan or other radiographic examination.
• For patients with T4b, R0 resection was expected to be achieved, including the necessary combined organ resection，by MDT discussion.
• No history of 5-Fu and platinum drug allergy.
• Adequate bone marrow function: Hb>9g/dl; PLT >100 x 10^9/l; WBC >3.5 x 10^9/l and ANC ≥1.5x10^9/l.
• Adequate hepatobiliary function: ASAT (aspartate aminotransferase) and ALAT (alanine aminotransferase) of 2.5 x ULN (upper limits of normal) or less, Alkaline phosphatase of 2.5 x ULN or less, total bilirubin 1.5 x upper normal level or less.
• Adequate renal biochemistry: GFR >50 ml/min calculated by the Wright or Cockroft formula or EDTA clearance >70 ml/min.
• For female and of childbearing potential, patient must have a negative pregnancy test ≤72hours prior to initiating study treatment and agree to avoid pregnancy during and for 6 months after study treatment. For male with a partner of childbearing potential, patient must agree to use adequate, medically approved, contraceptive precautions during and for 90 days after the last dose of study treatment
• Patient able and willing to provide written informed consent for the study.

Exclusion Criteria:

• Patients with lynch syndrome
• Rectal cancer located 10 cm or less from the anal verge.
• Any patient for whom radiotherapy is advised by the MDT.
• Patient with evidence of distant metastases or peritoneal nodules (M1).
• Severe intestinal complications on initial clinical or imaging assessment: perforation, obstruction, uncontrollable bleeding.
• Another serious medical condition judged to compromise ability to tolerate neoadjuvant therapy and/or surgery.
• Pre-existing or concurrent other malignancies (including concurrent colon cancer), except for cured basal cell carcinoma of the skin and carcinoma in situ of the cervix.
• Pregnant or breastfeeding women.
• Patients with severe cardiovascular disease and diabetes mellitus that cannot be easily controlled.
• Persons with mental disorders.
• Patients with severe infections.
• Patients on thrombolytic/anticoagulant therapy, bleeding quality or coagulation disorders; or aneurysms, strokes, transient ischemic attacks, arteriovenous malformations in the past year.
• Previous history of renal disease with urine protein on urinalysis or clinically significant renal function abnormalities.