Firefighters were called out after the fire started in the apartment, on the first floor of a red-brick house in the town of Hellemmes, near Lille.
But the woman and her two-year-old granddaughter and five-year-old grandson were already unconscious when they were found by their mother, returning from an errand. All three died from smoke inhalation.
"Their mother returned home, opened the door and found them," deputy mayor Evelyne Ledez told AFP.
"When we arrived the mother had already brought her children out of the flat," added chief rescuer Alain Chuffart.
"We brought their grandmother out and tried to revive them for about an hour", but the three had already stopped breathing.
The cause of the fire, which apparently started on a sofa and was confined to the living room, was not immediately known, Hellemmes mayor Frederic Marchand told AFP.