Purpose. The purpose of this prospective pilot study was to determine the efficacy of preoperative chemotherapy with six cycles of FOLFOX 6 (without radiation therapy) followed by radical surgery followed by six additional cycles ofFOLFOX6 for patients with stage II/III rectal cancer. Patients and Methods. From January 2010 to January 2014, patients with locally advanced rectal cancer who met the eligibility criteria were enrolled in this study. Patients received FOLFOX 6 chemotherapy comprising oxaliplatin and leucovorin calcium i.v. over 2 hours on day 1, then bolus, and then continuous fluorouracil i.v. over 46 hours on days 1 and 2. Treatment was repeated every 14 days for 6 courses followed by radical surgery followed by additional 6 cycles of FOLFOX 6. Results. In total, 45 patients were enrolled in this study. In the preoperative re-evaluation, the overall response rate was 68.8% (clinical complete response was 4.4%, and the partial response was 64.4%). There were 14 cases (31.2%) of stable disease. No patients had progressive disease. Postoperatively, the pathologic complete response ratewas8of45 (17.8%;95% confidence interval [CI]: 8.9%–28.9%). The median follow-up was 29 months (range 9–54 months). The actuarial 3-year overall survival and disease-free survival rates for all patients were 80.8% (standard error, 1.877; 95% CI: 69.3%–92.3%) and 67.9% (standard error, 2.319; 95% CI: 54.3%–81.5%), respectively. Conclusion. Neoadjuvant chemotherapy (FOLFOX) without radiotherapy is active and safe but cannot be considered a standard of care until the results of prospective randomized phase III trials are available.