FOLFOXIRI for Neoadjuvant Treatment of High-risk Locally Advanced Colorectal Cancer

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.