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Background Docetaxel–cisplatin and 5-fluorouracil (TPF) chemotherapy (days 1–21) represents a standard but toxic regimen for advanced head and neck cancer (HNC). We report a retrospective monocentric study evaluating the safety and the efficacy of a dose-dense modified TPF (mTPF) regimen (days 1–14) in patients with stage III–IV HNC. Methods Thirty-seven patients retrospectively included from May 2011 to May 2014 were treated with a bimonthly dose-dense mTPF regimen (40 mg/m 2 docetaxel, 40 mg/m 2 cisplatin or AUC2 carboplatin, folinic acid 400 mg/m 2 for 2 h, bolus 5-FU 400 mg/m 2 for 10 min and 5-FU 1,000 mg/m 2 /day) by continuous infusion over 46 h). Results Chemotherapy was used as induction or palliative treatment in 12 and 25 patients, respectively, with a median age of 60 years (range 46−83). Median follow-up time was 7.4 months (2.53–16.7 months). There was no intestinal toxicity in 25 patients (68 %). Grade 3–4 hematological toxicity was noticed for 5 (13.5 %) patients. Granulocyte-colony stimulating factor was used as primary prophylaxis in 30 patients (81 %). After at least 4 delivered cycles, complete responses, partial responses and stable diseases were reported in 5 (15 %), 13 (39 %) and 5 (15 %) of the 33 evaluable patients, respectively, yielding an objective response rate of 54.5 % (39 % for palliative chemotherapy and 90 % for induction chemotherapy). Conclusion Dose-dense mTPF (days 1–14) is safe and seems to be as effective as TPF (days 1–21). Future prospective trials are required to confirm our results.