Background: IC with docetaxel/cisplatin/fluorouracil (TPF) is superior to PF in organ preservation. Bioradiotherapy (BRT) is superior to RT alone in the loco-regional control of locally-advanced head and neck tumors. The aim of our study was to evaluate the efficacy and safety of IC followed by BRT for functional larynx preservation. Methods: Phase II, open-label, multicenter study in patients with stage III-IVA laryngeal carcinoma candidates to total laryngectomy (TL). Study was designed to evaluate the laryngo-esophageal dysfunction–free survival (LEDFS) rate at 3 years. Using the one arm survival sample size program (SWOG), calculated recruitment: 94 patients (α .05; ß .1). Critical value > 59%. Patients received 3 cycles of IC with TPF (75/75/750 mg/m²): those who responded received conventional BRT (70 Gy/7 weeks) with cetuximab. Patients without response underwent TL + RT. Neck dissection was planned in patients with residual nodal disease at 2 months after BRT. Results: A total of 93 patients started TPF from October/2008 to February/2011: median age 59.4; 92% male; all PS: 0-1; 35% glottis / 65% supraglottis; 51% stage III / 49% IVA. Response to IC on larynx target lesion: 37 (40%) CR, 34 (37 %) PR, 8 (9 %) SD, 2 (2%) PROG and 12 (13%) not evaluated (2 death, 6 AEs, 3 missing, 1 lost follow-up). Overall response 72 (86 %). 73 (78%) patients followed by BRT: 68 as per protocol, but 2 with only SD and 3 without any response evaluation. Median follow-up: 48 months. 3-year actuarial rates: LEDFS: 69.5% (95%CI: 60-79%); laryngectomy-free survival: 71.2% (95% CI: 61-81%); overall survival: 77.2% (95%CI: 69-86%); disease-free survival: 47.9% (95%CI: 38-58%). TL was performed in 18 patients: 9 (9.7 %) after preservative treatment failure and 9 (9.7 %) in the follow-up (recurrences). The toxicity observed during both IC and BRT were as expected, with only 1 toxic related death (local bleeding during BRT). Conclusions: LEDFS rate was clearly higher than the critical value and with an acceptable toxicity with this protocol, so it is warranted to move to a phase III trial. Clinical trial information: 2008-000332-40.