Background: It is still controversial for colon cancer patients with unresectable metastases whether to resect the primary tumor when there are no symptoms of primary lesion. Methods: This is an open-label, single-center, prospective, randomized, controlled phase II trial. Colon cancer patients aged 18-80 years with unresectable metastases at enrollment will be randomly allocated to either resection group (group A) or chemotherapy group (group B), and stratified by tumor response and number of organ metastases, after receiving induction chemotherapy with 4 cycles of XELOX or 6 cycles of mFOLFOX6, excluding those with disease progression, lesions radically resectable, or primary lesion unresectable. Patients in group A received resection of primary lesion and then continued chemotherapy, and patients in group B just continued chemotherapy, both up to 4 cycles of XELOX or 6 cycles of mFOLFOX6, and capecitabine maintenance afterwards. If progression occurs 3 months after discontinuation of oxaliplatin and toxicity has recovered to grade I, the original regimen can be applied again. The primary endpoint was TFS (time to failure of strategy, defined as the time from randomization to secondary progression in patients received re-introduce of the induction chemotherapy regimen, or to first progression in patients without re-introduce of the original regimen). The secondary endpoints included progression-free survival (PFS, the time from randomization to first progression), overall survival (OS, the time from enrollment to death), and adverse events (AEs). Efficacy data were analyzed on an intention-to-treat (ITT) basis. This study is registered with ClinicalTrials.gov, number NCT02291744. Results: Between April, 2015, and July, 2020, 140 patients were enrolled, and 54 patients withdrew due to colon obstruction (16), perforation (1), disease progression (22), death (1), radical resection (3), or other reasons (11). Finally, 86 patients were randomized into group A (n = 42) or group B (n = 44). The median TFS was 143 days (95%CI: 104.9-181.1) in group A, and 196 days (95%CI: 96.5-295.5) in group B (HR:0.930 95%CI:0.589-1.468, p = 0.755). The median PFS was 147 days (95%CI: 105.7-188.3) in group A, and 206 days(95%CI:180.9-231.1) in group B (HR:0.831, 95%CI:0.522-1.323, p = 0.436). The median OS was 530 days (95%CI: 308.9-751.1) in group A, and 779 days (95%CI:626.3-931.7) in group B (HR:0.948 95%CI:0.554-1.622, p = 0.845). The incidence of treatment-related AEs was similar between two groups. Conclusions: Resection of primary tumor after induction chemotherapy could not bring survival benefits. It’s not recommended for patients without symptoms of primary lesion to receive primary tumor resection, but it also requires individualized treatment as colon obstruction or perforation occurred in some patients. Clinical trial information: NCT02291744