Background: The start of chemotherapy usually requires a delay of about 4 weeks after surgical resection of colorectal cancer. However, there is no evidence for the required length of this delay interval. In addition, there is a chance that a patient may die because postoperative chemotherapy was not started soon enough and a metastatic tumor was able to develop rapidly. We have previously reported the first pilot study to determine the safety and feasibility of an early start of chemotherapy after resection of primary colorectal cancer with distant metastases. We therefore conducted a next study to determine the safety and efficacy of the early start of chemotherapy after the resection of colorectal cancer with distant metastases. Methods: The Pearl Star 02 study was a prospective and single-arm trial. They received XELOX therapy (130 mg/m2 of oxaliplatin on day 1 plus 1,000 mg/m2 of capecitabine twice daily on days 1–14) on the 7th postoperative day and XELOX+bevacizumab (7.5 mg/kg of bevacizumab on day 1) after the 2nd cycle of chemotherapy. Results: A total of 20 patients were enrolled from September 2011 to June 2015. Baseline characteristics included a median age of 64 years (range: 43-72) for 15 men and 5 women. The procedures included right hemicolectomy in 6 patients, sigmoidectomy in 3 patients, high anterior resection in 3 patients, low anterior resection in 2 patients, and Hartmann procedure in 6 patients. All patients started chemotherapy on postoperative day 7. Grade 3 or higher hemotoxicity and grade 3 or higher non-hematological toxicity was noted in 5.0 % and 25.0 % of patients, respectively. Postoperative complications were observed in 2 patients (superficial incisional surgical site infection and Ileus). Median progression-free survival was 14.9 months. Overall response rate was 75%. Conclusions: An early start of chemotherapy after surgery is safe and effective. These findings suggest possible changes in the start time of chemotherapy after surgery in the future. However, further studies are certainly needed to confirm these findings. Clinical trial information: UMIN000006310.