Background: To report the long-term survival outcomes of the ADORE, a randomized controlled trial, compared adjuvant FOLFOX vs FL in patients with resected rectal cancer whose pathologic stages of ypII/III after preoperative chemoradiotherapy (CRT). Methods: This is a randomized phase II study accrued patients with curatively resected rectal cancer patients whose postoperative ypStage II/III after preoperative CRT with fluoropyrimidines alone. Patients were randomly assigned (1:1) to receive adjuvant chemotherapy either with FL or FOLFOX for 4 months. Randomization was centrally coordinated and stratified by the ypStage and participating sites. The primary endpoint was disease-free survival (DFS). Results: A total of 321 patients were randomly assigned between Nov 2008 and Jun 2012; 161 patients to FL and 160 to FOLFOX. At a median follow-up of 74.1 months (IQR, 56.2 – 88.0), 6-year DFS rate was 68.2% in the FOLFOX arm vs 56.8% in the FL arm with an adjusted hazard ratio (HR) of 0.63 (95% CI, 0.43–0.93, p= 0.018) by intention-to-treat analysis. In the subgroup analysis for DFS, patients with ypStage III (HR 0.59 [0.38-0.92], p= 0.019), ypN1b (HR 0.35 [0.14-0.83], p= 0.017), ypN2 (HR 0.47 [0.22-0.99], p= 0.048), high grade histology (HR 0.28 [0.08-0.97], p= 0.045), minimally regressed tumor (0.40 [0.19-0.85], p= 0.016), absence of lymphovascular (HR 0.55 [0.34-0.88], p= 0.013) or perineural invasion (HR 0.53 [0.33-0.86], p= 0.01), male gender (HR 0.62 [0.39-0.98], p= 0.039), and younger than 65 years (HR 0.64 [0.42-0.97], p= 0.034) benefited more from FOLFOX than FL. The 6-year overall survival (OS) rate was 78.1% in the FOLFOX arm vs 76.4% in the FL arm (HR 0.73 [0.45-1.19], p= 0.21). In the subgroup analysis for OS, those with ypN2 (HR 0.42 [0.18-0.96], p= 0.04) and minimally regressed tumor (HR 0.42 [0.19-0.97], p= 0.043) benefited from FOLFOX than FL. Conclusions: Adjuvant FOLFOX clearly demonstrated improved DFS in rectal cancer patients with ypStage II/III after preoperative CRT. Subgroup analyses provided additional information on the selection of adjuvant candidates. Clinical trial information: NCT00807911