Very-early-onset inflammatory bowel disease (VEO-IBD) has a distinct phenotype and should be considered a specific entity. VEO-IBD presents with very severe clinical pictures and is frequently known by an indeterminate colitis whose clinical remission is unmanageable. This study examines the case of a neonate with VEO-IBD, not responding to medical and surgical treatment. A 7-day-old Iranian female neonate presented with severe bloody diarrhea, poor feeding, abdominal distention, and dehydration suggesting severe proctocolitis due to an allergy to the protein in cow’s milk. The condition did not respond to the elimination of diet for 1 month. Infections, celiac disease, and cystic fibrosis were excluded. Immunological investigations were negative, but antineutrophil cytoplasmic antibodies were positive. Due to the neonate’s persistent symptoms and failure to thrive, upper and lower endoscopies were performed, showing ulcerative colitis. At the age of 4 months, she presented with signs and symptoms of toxic colitis and acute intestinal perforation, which prompted an emergency laparotomy. Due to the necrosis of the colon, hemicolectomy and colostomy were done. The patient was resuscitated and rehabilitated and was given glucocorticoid and mesalamine. We believe that the incidence of this problem is increasing, as is shown by the rise in the number of children under 10 years old being diagnosed. These patients require more aggressive therapeutic interventions than older IBD patients to achieve complete remission because they are more likely to have extensive colonic disease.