Desmoid tumors are benign, slow-growing mesenchymal tumors. Aggressiveness is local with no potential for metastasis or dedifferentiation. The treatment is challenging, particularly in the case of huge intra-abdominal locations. We, herein, report on a 21-year-old patient with a giant intra-abdominal desmoid tumor occupying substantially the entire abdominal cavity. After failure of a first-line combination of celecoxib and tamoxifen, the patient was given doxorubicin-dacarbazine chemotherapy. The treatment was well tolerated, and rapidly, the clinical digestive symptoms improved. After 6 cycles, the computed tomography scan showed a partial response (regression of tumor volume by 55%). During follow-up, the tumor continued to regress: 25 months after the end of chemotherapy, the tumor volume had regressed by 95% when compared to the start of computed tomography and by 90% when compared to the end of chemotherapy. Thirty-three months after the diagnosis, the patient is alive without any symptom. Our case provides further evidence of the remarkable efficacy of a doxorubicin-dacarbazine regimen, especially in function- or life-threatening situations where a rapid response is required. We review the literature and discuss the challenging issue regarding treatment of desmoid tumors.