PURPOSE: To report the long-term follow-up data and determine the toxicity rate concerning patients with locally advanced rectal cancer (LARC) treated with an intensified neoadjuvant treatment regimen. PATIENTS AND METHODS: Patients with histologically proven stage II to III adenocarcinoma of the rectum were included and treated with a trimodal approach. Intensified neoadjuvant treatment (chemoradiotherapy [CRT]) consisted of radiotherapy (total dose 50.4/54 Gy) and concomitant oxaliplatin (50 mg/m(2)/week) and 5-fluorouracil (200 mg/m(2)/5 daily continuous infusion). Surgery was planned 7 to 9 weeks after the end of CRT. Adjuvant chemotherapy was recommended in those patients with lymph node metastasis at diagnosis. RESULTS: One hundred patients (median age, 64 years) were eligible. Overall, the 5-year overall survival and disease-free survival (DFS) were 76.4% and 74.5%, respectively. CRT was well tolerated, with only 17% grade 3/4 acute toxicity. Twenty-four patients (24%) had a pathologic complete response (pCR), and only 1 patient had perioperative metastasis. The 5-year DFS were 95.7% and 66.7% for pCR and no-pCR tumor histology, respectively (P = .0275). CONCLUSION: Although oxaliplatin is not considered to be a standard treatment, the high 5-year rate of overall survival and DFS, the low severe toxicity rates, and the effective benefit on pCR and perioperative metastasis support an intensified treatment regimen for LARC.