Background: In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant chemotherapy with FOLFOX or CAPOX regimens has become a standard treatment. However, 20 to 30 % of these patients will develop distant metastasis, which ultimately result in death. Perioperative chemotherapy is a promising strategy with potential benefits that could be more effective at eradicating micrometastases. Moreover, shrinking tumor before surgery not only facilitate removal of all the tumor by the surgeon but also reduce tumor cell spreading during the procedure. With recent advances in radiology, preoperative computed tomography is a robust method for measuring the depth of tumor invasion and identifying the CC patients with poor prognosis, who may benefit from perioperative chemotherapy. We conducted the present randomized study to explore whether perioperative chemotherapy with FOLFOX or CAPOX regimens compared with postoperative chemotherapy could improve disease-free survival in patients with radiologically staged, locally advanced, but resectable colon cancer. Methods: This trial is a two-arm, multicenter, open labelled, prospective, randomized phase III studies. 738 eligible patients with locally advanced (T4 or T3 with extramural depth≧5 mm) CC patients will be randomly assigned, in a 1:1 ratio, to receive either perioperative (6 cycles of mFOLFOX6 or 4 cycles of CAPOX followed by surgery and a further 6 cycles of mFOLFOX6 or 4 cycles of CAPOX) or postoperative chemotherapy (surgery followed by 12 cycles of mFOLFOX6 or 8 cycles of CAPOX). The primary objective of this study is 3-year disease-free survival. Secondary objectives are efficacy in terms of R0 resection rate, overall survival (OS), relapse-free survival (RFS), down-staging of primary tumors, and tolerability of perioperative therapy and postoperative complications. Clinical trial information: NCT02572141