In the 17th and 18th centuries, British, Portuguese, French and Spanish explorers continued to pass through the estuary. The main economic activities are fishing and the fur trade.

The King of France entrusts the expansion of colonization to a few merchants, granting them a monopoly on the fur trade. However, these merchants choose to maximize the profits of the trade while neglecting settlement.

As of 1615, religious missionaries joined with laymen launch exploration and trading expeditions. The missionaries help establishing the settlements and convert the Indigenous peoples to the Catholic religion.

At Pointe-aux-Anglais, near the Bic, merchants from La Rochelle violate the monopoly granted by the king and use alcohol to lure the First Nations to trade goods with them.

Towards the end of the 17th century, the First Nations were forced to share their territory with Europeans as they slowly settled in the region. Increased contact between the two populations led to epidemics, which resulted in a mortality rate of up to 90% among the Indigenous peoples, depending on the area.

The Seigneurie du Bic was granted in 1675 by Governor Frontenac to Charles Denys de Vitré. He hired workers to harvest herring, salmon and shad. These fish were put into barrels and sold in Québec and overseas.

The concession allows Vitré to clear a few dozen acres of forest to erect buildings and grow the crops to feed the settlers.

The cattle help the settlers with clearing and plowing in the settlement areas.

Settlement in the Lower St-Lawrence progresses slowly. The settlers are established mainly along the river.They rub shoulders with Indigenous people who also pass through the area.

The Seigneury of Rimouski is acquired by René Lepage in exchange for his land on Orleans Island. He settles there in 1696. Around 1700, the Lower St-Lawrence has about thirty French-speaking inhabitants.